The use of the new heat-not-burn electronic cigarettes increases pulmonary oxidative stress, damages DNA and alters ultrastructural lung airways

Recently, the Food and Drug Administration authorized the Heat not Burn (HnB) Tobacco Heating System for marketing as Modified Risk Tobacco. However, to date there are no robust evidence of a lower health risk for consumers. The present study was conceived to help fill the knowledge gap on toxicological outcomes associated with HnB by exploring its effects on lung structure along with its genotoxic and co-carcinogenic potential. Male Sprague-Dawley rats were exposed using a whole-body mode. The puff profile consisted in (5 s on, 15 s off, 5 s on) with an airflow of 4 L/min. The puff profile and flow rate were determined in accordance with previous studies on e-cigarettes. Daily treatments were scheduled for five consecutive days/week followed by two days off, for 4 consecutive weeks. Here, we identified irritating and carcinogenic compounds including aldehydes and polycyclic aromatic hydrocarbons in the HnB mainstream as sign of incomplete combustion and degradation of tobacco. Our results show that HnB use increases tissue free radicals concentration and it promotes severe remodeling of smaller and largest rat airways, oxidative DNA breakage damage. HnB exposure triggered an inflammatory response with higher levels of pro-inflammatory mediators such as TNF-α; CCL3 CSF2 and COX commonly observed in tobacco smoking models. In addition, the exposed animals showed increased expression of the mitogen activated protein kinase stimulating pathway that is involved in cancer progression induced by conventional tobacco smoke. HnB has been proposed as a safer alternative to conventional cigarettes, due to reduced concentration of various harmful constituents typical of traditional tobacco smoke. However, our findings confirm that HnB mainstream contains byproducts of pyrolysis and thermogenic degradation, the same harmful constituents of traditional cigarette smoke, and for the first time, we demonstrate that it causes grave lung damage and promotes factors that increase the risk of cancer in the animal model.